IL-12 down-regulates autoantibody production in mercury-induced autoimmunity.
In genetically susceptible H-2s mice, subtoxic doses of mercuric chloride (HgCl2) induce a complex autoimmune syndrome characterized by the production of anti-nucleolar IgG Abs, lymphoproliferation, increased serum levels of IgG1 and IgE Abs, and renal Ig deposits. Mercury-induced autoimmunity in H-2s mice provides a useful model for chemically related autoimmunity in humans. The increase in serum IgG1 and IgE, which are under IL-4 control, suggests a role for the Th2 subset in this syndrome. The IL-12 cytokine induces T cell proliferation and IFN-gamma production and is necessary for differentiation of naive T cells into the Th1 subset. To gain an understanding of T cell control in this syndrome and, in particular, Th1/Th2 regulation, we assessed the effect of IL-12 administration in mercury-induced autoimmunity. Groups of A.SW mice (H-2s) received HgCl2 plus IL-12, HgCl2 alone, or IL-12 alone. IL-12 treatment resulted in a dramatic reduction of the anti-nucleolar Ab titers. IL-12 also inhibited the HgCl2-induced serum IgG1 increase, but, in contrast, did not significantly affect IgE induction in this model. This observation may be related to our unexpected finding that IL-12 further potentiated the HgCl2-triggered IL-4 induction in this model. The levels of renal Ig deposits were similar in mice receiving HgCl2 alone or HgCl2 plus IL-12. Our results indicate that IL-12 can down-regulate the autoimmune component of this experimental syndrome and that the various manifestations of mercury-induced autoimmunity are independently regulated.
Bagenstose
L M
LM
Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Salgame
P
P
Monestier
M
M
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis* / Q000187:drug effects; D001327:Autoimmune Diseases / Q000139:chemically induced* / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects; D002466:Cell Nucleolus / Q000276:immunology; D015536:Down-Regulation / Q000276:immunology*; D005260:Female; D007073:Immunoglobulin E / Q000097:blood / Q000187:drug effects; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007279:Injections, Subcutaneous; D018664:Interleukin-12 / Q000008:administration & dosage / Q000494:pharmacology*; D015847:Interleukin-4 / Q000096:biosynthesis; D007668:Kidney / Q000276:immunology / Q000378:metabolism; D018655:Lymphocyte Count / Q000187:drug effects; D008627:Mercuric Chloride / Q000633:toxicity*; D051379:Mice; D008805:Mice, Inbred A; D013154:Spleen / Q000166:cytology
D000276:Adjuvants, Immunologic; D000974:Antibodies, Antinuclear; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D018664:Interleukin-12; D015847:Interleukin-4; D007073:Immunoglobulin E; D008627:Mercuric Chloride